HIV-1 mediates rapid apoptosis of lymphocytes from human CD4 transgenic but not normal rabbits

Normal rabbit lymphocytes can be infected with HIV-1 although infection is much less efficient than in human lymphocytes. When peripheral blood mononuclear cells (PBMC) from rabbits transgenic for human CD4 (HuCD4) were exposed to HIV-1, enhanced infection and a rapid depletion of lymphocytes were observed. Cell death in the infected cultures occurred via apoptosis, but no similar effect was seen in nontransgenic rabbit PBMC cultures. Induction of apoptosis in HuCD4-expressing cells required virus replication; heat-inactivated virus or recombinant viral proteins had no effect on cell viability. Expression of the Fas antigen was increased in HIV-1-infected CD4+ rabbit lymphocytes. Characterization of the infected PBMC cultures revealed that apoptosis occurs both in HuCD4+ and HuCD4- cells, indicating that bystander cells are killed. These data define a requirement for HuCD4 in initiation, but not the spread, of HIV-1-induced apoptosis in rabbit PBMC and provide a model to probe mechanisms leading to lymphocyte depletion in HIV-1 infection.